Cell-specific effects of miR-221/222 in vessels: molecular mechanism and therapeutic application.
Cell-specific effects of miR-221/222 in vessels: molecular mechanism and therapeutic application.
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DOI：
10.1016/j.yjmcc.2011.11.008
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发表时间：
2012-01
影响因子：
5
通讯作者：
Zhang C
中科院分区：
文献类型：
--
作者：
Liu X;Cheng Y;Yang J;Xu L;Zhang C
microRNAs（miRNAs）是一种非编码RNA，几乎影响生物学和疾病的各个方面。迄今为止，miRNAs在心血管系统中的细胞特异性作用尚未确定。本研究比较了miR-221和miR-222（miR-221/222）在血管平滑肌细胞（VSMCs）和血管内皮细胞（ECs）中的细胞功能。在培养的细胞中，我们发现miR-221/222对VSMCs和EC的增殖、迁移和凋亡的影响是相反的。在VSMC中，miR-221/222具有促增殖、促迁移和抗凋亡的作用。相反，miR-221/222在EC中具有抗增殖、抗迁移和促凋亡的作用。两种细胞类型之间靶基因p27（kip1）、p57（kip2）和c-kit的不同表达谱可能与相反的效应有关。最后，在球囊损伤的大鼠颈动脉中体内验证了miR-221/222的相反细胞效应，如通过新生内膜生长和再内皮化的不同结果所证明的。结果表明，miR-221/222在血管壁中的生物学功能是细胞特异性的。miR-221/222对VSMC和EC的相反细胞效应可能在许多血管疾病（例如动脉粥样硬化和血管成形术后再狭窄）中具有重要的治疗应用。
MicroRNAs (miRNAs) are noncoding RNAs that impact almost every aspect of biology and disease. Until now, the cell-specific effects of miRNAs in cardiovascular system have not been established. In the current study, the cellular functions of miR-221 and miR-222 (miR-221/222) in vascular smooth muscle cells (VSMCs) and vascular endothelial cells (ECs) were compared. In cultured cells, we identified that the effects of miR-221/222 on proliferation, migration, and apoptosis are opposite between VSMCs and ECs. In VSMCs, miR-221/222 had effects of pro-proliferation, pro-migration, and anti-apoptosis. In contrast, miR-221/222 had effects of anti-proliferation, anti-migration, and pro-apoptosis in ECs. The different expression profiles of their target genes, p27(Kip1), p57(kip2), and c-kit between the two cell types might be related to the opposite effects. Finally, the opposite cellular effects of miR-221/222 were verified in vivo in balloon-injured rat carotid artery as demonstrated by different consequences in neointimal growth and re-endothelialization. The results suggest that the biological functions of miR-221/222 in vascular walls are cell-specific. The opposite cellular effects of miR-221/222 on VSMCs and ECs may have important therapeutic applications in many vascular diseases such as atherosclerosis and restenosis after angioplasty.
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影响因子：
20.1
作者：
Kuehbacher, Angelika;Urbich, Carmen;Dimmeler, Stefanie
通讯作者：
Dimmeler, Stefanie
影响因子：
4.8
作者：
Davis, Brandi N.;Hilyard, Aaron C.;Hata, Akiko
通讯作者：
Hata, Akiko
影响因子：
56.9
作者：
Farh, KKH;Grimson, A;Bartel, DP
通讯作者：
Bartel, DP
影响因子：
5.3
作者：
Kotha, Jayaprakash;Zhang, Chunxiang;Jennings, Lisa K.
通讯作者：
Jennings, Lisa K.
影响因子：
4.8
作者：
Flores-Rios, Xacobe;Marzoa-Rivas, Raquel;Castro-Beiras, Alfonso
通讯作者：
Castro-Beiras, Alfonso